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Chemokine gene expression influences metastasis and survival time of female dogs with mammary carcinoma.
Veterinary Immunology and Immunopathology ( IF 1.8 ) Pub Date : 2020-06-13 , DOI: 10.1016/j.vetimm.2020.110075
Harsha Ariyarathna 1 , Neroli Thomson 1 , Danielle Aberdein 1 , John S Munday 1
Affiliation  

Chemokines are signaling proteins secreted by immune cells which regulate leukocyte trafficking. The aberrant expression of chemokines and their receptors by neoplastic cells influences the behaviour of many human cancers. This study evaluated gene-expression of the chemokines: CCL5, CXCL10, CXCL12 and the chemokine receptors: CXCR3, CXCR4, CXCR7, CCR4, CCR9 in 41 histologically-malignant, outcome-known, canine mammary tumours. These chemokines and chemokine receptors were selected as all were previously shown to influence the behaviour of human breast cancers. The expression of chemokines CCL5 and CXCL12 were significantly higher in tumours which subsequently metastasised than tumours that did not metastasise (p < 0.05). Increased expression of these chemokines was also correlated with shorter survival times of the dogs (CCL5: rs = –0.40, p = 0.02, CXCL12: rs = –0.40, p = 0.03) while CCL5 was independently prognostic of survival times (p = 0.026). A significantly higher proportion of tumours that subsequently metastasised expressed CXCR3 (p = 0.037), CXCR4 (p = 0.026), CXCR7 (p = 0.025) and CCR9 (p = 0.039) receptors while the survival times of the dogs with tumours that expressed CXCR4 (p = 0.045) and CCR9 (p = 0.039) receptors were significantly shorter than dogs with tumours that did not express these receptors. Chemokine and chemokine receptor gene-expression has not been previously correlated with disease outcome of canine mammary tumours. These findings indicate that altered expression of chemokines and their receptors influences the behaviour of canine mammary tumours suggesting a potential role of them as prognostic markers or therapeutic targets.



中文翻译:

趋化因子基因表达影响雌性乳腺犬的转移和存活时间。

趋化因子是调节白细胞运输的免疫细胞分泌的信号蛋白。肿瘤细胞趋化因子及其受体的异常表达影响许多人类癌症的行为。这项研究评估了41种组织学恶性,已知结局的犬乳腺肿瘤中趋化因子CCL5,CXCL10,CXCL12和趋化因子受体CXCR3,CXCR4,CXCR7,CCR4,CCR9的基因表达。选择这些趋化因子和趋化因子受体,因为所有这些因子先前已显示出会影响人类乳腺癌的行为。在随后转移的肿瘤中,趋化因子CCL5和CXCL12的表达明显高于未转移的肿瘤(p<0.05)。这些趋化因子的表达增加还与狗的生存时间较短有关(CCL5:r s = –0.40,p = 0.02,CXCL12:r s = –0.40,p = 0.03),而CCL5独立地预测了生存时间(p = 0.026)。随后转移的肿瘤中表达CXCR3(p = 0.037),CXCR4(p = 0.026),CXCR7(p = 0.025)和CCR9(p = 0.039)受体的比例明显更高,而患有表达CXCR4的狗的存活时间(p = 0.045)和CCR9(p= 0.039)受体明显短于不表达这些受体的狗。趋化因子和趋化因子受体基因的表达以前没有与犬乳腺肿瘤的疾病结果相关。这些发现表明趋化因子及其受体表达的改变会影响犬乳腺肿瘤的行为,提示它们可能作为预后标志物或治疗靶标。

更新日期:2020-06-24
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